Special Issue "Radiation and Cancers"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2011)

Special Issue Editor

Guest Editor
Prof. Dr. Ritsuko U. Komaki

Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Special Issue Information

Dear Colleagues,

I would like to invite you a very exciting issue entitled as "Radiation and Cancer" in Cancers.

X-Rays were discovered in 1985. Since then X-rays had been used in Europe, America and rest of the world in primitive planning and deliver for the cancer till recently. Parallel to the discovery of X-rays, Becquerel and Curie discovered radioactive material in 1998. During the early 1900s, radiobiological experiments were conducted with simple biologic systems corresponding with the development of radiation therapy. However it took long time to get adequate imaging studies to demonstrate location and extent of the cancer by computerized tomography (CT), magnetic resonant imaging (MRI), positron emission tomography (PET) and other functional or metabolic imaging. These imaging studies are essential to plan and deliver radiation treatment to kill cancer cells without causing excessive normal tissue toxicities and/or secondary malignancies. Now we are able to 3 dimensional conformal radiotherapy (3DCRT), 4 D-RT accounting time, Stereotactic Radiotherapy, Intensity Modulated Radiotherapy (IMRT) and particle Radiotherapy such as Proton and Carbon Iron. Discovery of mechanism of radiation resistant cells and development of radiation sensitizers including chemotherapy and molecular targeting treatment are essential to improve therapeutic ratio.

Our main goal is here to show how we plan and deliver Radiation Therapy for different type of Cancer with or without other modalities demonstrating less normal tissue toxicities and better outcome.

Hope you can join me.

Sincerely,

Ritsuko Komaki, M.D.
Guest Editor

Published Papers (13 papers)

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Research

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Open AccessArticle An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications
Cancers 2012, 4(2), 566-580; doi:10.3390/cancers4020566
Received: 12 April 2012 / Revised: 29 May 2012 / Accepted: 6 June 2012 / Published: 15 June 2012
Cited by 8 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), a/β and radiosensitivity a,
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In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), a/β and radiosensitivity a, were estimated. Other radiobiological models: EUD, BED, TCP, etc., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined a/β, a and Td are a/β = 8.1 ± 4.1 Gy, a = 0.22 ± 0.08 Gy−1, Td = 4.0 ± 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, i.e., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Distribution of Functional Liver Volume in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus in the 1st Branch and Main Trunk Using Single Photon Emission Computed Tomography—Application to Radiation Therapy
Cancers 2011, 3(4), 4114-4126; doi:10.3390/cancers3044114
Received: 22 September 2011 / Revised: 22 October 2011 / Accepted: 22 October 2011 / Published: 31 October 2011
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Abstract
Purpose: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal
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Purpose: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT) by exploring the relation of FLV in MV to radiation-induced liver disease (RILD). Methods and Materials: Clinical target volume (CTV) included main tumor and PVTT, and planning target volume (PTV) included CTV with a 10 mm margin. MV was defined as PTV–CTV. FLV ratio in MV was calculated as FLV in MV/MV × 100 (%). The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child–Pugh grade B) with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV × 100 (%). Results: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001). Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200–300 cm3, three with CTV of 500–600 cm3, and two with CTV of 1100–1200 cm3. The destructive ratio yielded a mean value of 24.2 ± 1.5%. Conclusions: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Carbon Ion Radiotherapy at the Gunma University Heavy Ion Medical Center: New Facility Set-up
Cancers 2011, 3(4), 4046-4060; doi:10.3390/cancers3044046
Received: 18 August 2011 / Revised: 30 September 2011 / Accepted: 13 October 2011 / Published: 26 October 2011
Cited by 29 | PDF Full-text (632 KB) | HTML Full-text | XML Full-text
Abstract
Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first patient
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Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first patient at Gunma University Heavy Ion Medical Center (GHMC) was initiated in March of 2010. The major specifications of the facility were determined based on the experience of clinical treatments at the National Institute of Radiological Sciences (NIRS), with the size and cost being reduced to one-third of those at NIRS. The currently indicated sites of cancer treatment at GHMC are lung, prostate, head and neck, liver, rectum, bone and soft tissue. Between March 2010 and July 2011, a total of 177 patients were treated at GHMC although a total of 100 patients was the design specification during the period in considering the optimal machine performance. In the present article, we introduce the facility set-up of GHMC, including the facility design, treatment planning systems, and clinical preparations. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Helical Tomotherapy in Children and Adolescents: Dosimetric Comparisons, Opportunities and Issues
Cancers 2011, 3(4), 3972-3990; doi:10.3390/cancers3043972
Received: 13 September 2011 / Revised: 7 October 2011 / Accepted: 17 October 2011 / Published: 25 October 2011
Cited by 3 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences
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Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1–24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac-based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Figures

Open AccessArticle Evaluation of Changes in Tumor Shadows and Microcalcifications on Mammography Following KORTUC II, a New Radiosensitization Treatment without any Surgical Procedure for Elderly Patients with Stage I and II Breast Cancer
Cancers 2011, 3(3), 3496-3505; doi:10.3390/cancers3033496
Received: 21 June 2011 / Revised: 2 September 2011 / Accepted: 5 September 2011 / Published: 9 September 2011
Cited by 5 | PDF Full-text (1709 KB) | HTML Full-text | XML Full-text
Abstract
We introduced non-surgical therapy with a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) into early stages breast cancer treatment. The purpose of this study was to examine changes in tumor shadows and microcalcifications on mammography (MMG)
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We introduced non-surgical therapy with a novel enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) into early stages breast cancer treatment. The purpose of this study was to examine changes in tumor shadows and microcalcifications on mammography (MMG) following KORTUC II for elderly patients with breast cancer. We also sought to determine whether MMG was useful in evaluating the therapeutic effect of KORTUC II. In addition to MMG, positron emission tomography-computed tomography (PET-CT) was performed to detect both metastasis and local recurrence. In all 10 patients, tumor shadows on MMG completely disappeared in several months following the KORTUC II treatment. The concomitant microcalcifications also disappeared or markedly decreased in number. Disappearance of the tumors was also confirmed by the profile curve of tumor density on MMG following KORTUC II treatment; density fell and eventually approached that of the peripheral mammary tissue. These 10 patients have so far have also shown neither local recurrence nor distant metastasis on PET-CT with a mean follow-up period of approximately 27 months at the end of September, 2010. We conclude that breast-conservation treatment using KORTUC II, followed by aromatase inhibitor, is a promising therapeutic method for elderly patients with breast cancer, in terms of avoiding any surgical procedure. Moreover, MMG is considered to be useful for evaluating the efficacy of KORTUC II. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre
Cancers 2011, 3(3), 3419-3431; doi:10.3390/cancers3033419
Received: 15 August 2011 / Revised: 24 August 2011 / Accepted: 25 August 2011 / Published: 1 September 2011
Cited by 4 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
Purpose: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. Methods and Materials: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with
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Purpose: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. Methods and Materials: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5–8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8-years post treatment. Results: All patients completed radiotherapy without any treatment breaks. The 8-year risks of ≥ Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of ≥ Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. Conclusions: These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord
Cancers 2011, 3(2), 2421-2443; doi:10.3390/cancers3022421
Received: 14 March 2011 / Revised: 20 April 2011 / Accepted: 10 May 2011 / Published: 18 May 2011
Cited by 4 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text
Abstract
Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology.
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Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ2-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint. Full article
(This article belongs to the Special Issue Radiation and Cancers)

Review

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Open AccessReview Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies
Cancers 2012, 4(1), 307-322; doi:10.3390/cancers4010307
Received: 3 January 2012 / Revised: 21 February 2012 / Accepted: 6 March 2012 / Published: 14 March 2012
Cited by 4 | PDF Full-text (322 KB) | HTML Full-text | XML Full-text
Abstract
For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC)
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For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG)
Cancers 2011, 3(4), 4061-4089; doi:10.3390/cancers3044061
Received: 5 August 2011 / Revised: 8 October 2011 / Accepted: 21 October 2011 / Published: 28 October 2011
Cited by 3 | PDF Full-text (244 KB) | HTML Full-text | XML Full-text
Abstract
Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive
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Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy), are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview The Utility of Proton Beam Therapy with Concurrent Chemotherapy for the Treatment of Esophageal Cancers
Cancers 2011, 3(4), 4090-4101; doi:10.3390/cancers3044090
Received: 7 September 2011 / Revised: 17 October 2011 / Accepted: 20 October 2011 / Published: 28 October 2011
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Abstract
The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality
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The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Role of Radiation Therapy in the Management of Renal Cell Cancer
Cancers 2011, 3(4), 4010-4023; doi:10.3390/cancers3044010
Received: 8 August 2011 / Revised: 11 October 2011 / Accepted: 19 October 2011 / Published: 26 October 2011
Cited by 14 | PDF Full-text (100 KB) | HTML Full-text | XML Full-text
Abstract
Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC,
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Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Combined Hyperthermia and Radiotherapy for the Treatment of Cancer
Cancers 2011, 3(4), 3799-3823; doi:10.3390/cancers3043799
Received: 15 July 2011 / Revised: 23 September 2011 / Accepted: 23 September 2011 / Published: 30 September 2011
Cited by 18 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in­tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects.
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Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in­tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, car­diac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threat­ening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Strategies To Assess Hypoxic/HIF-1-Active Cancer Cells for the Development of Innovative Radiation Therapy
Cancers 2011, 3(3), 3610-3631; doi:10.3390/cancers3033610
Received: 4 August 2011 / Revised: 12 August 2011 / Accepted: 9 September 2011 / Published: 15 September 2011
Cited by 7 | PDF Full-text (272 KB) | HTML Full-text | XML Full-text
Abstract
Local tumor recurrence and distant tumor metastasis frequently occur after radiation therapy and result in the death of cancer patients. These problems are caused, at least in part, by a tumor-specific oxygen-poor microenvironment, hypoxia. Oxygen-deprivation is known to inhibit the chemical ionization of
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Local tumor recurrence and distant tumor metastasis frequently occur after radiation therapy and result in the death of cancer patients. These problems are caused, at least in part, by a tumor-specific oxygen-poor microenvironment, hypoxia. Oxygen-deprivation is known to inhibit the chemical ionization of both intracellular macro-molecules and water, etc., and thus reduce the cytotoxic effects of radiation. Moreover, DNA damage produced by free radicals is known to be more repairable under hypoxia than normoxia. Hypoxia is also known to induce biological tumor radioresistance through the activation of a transcription factor, hypoxia-inducible factor 1 (HIF-1). Several potential strategies have been devised in radiation therapy to overcome these problems; however, they have not yet achieved a complete remission. It is essential to reveal the intratumoral localization and dynamics of hypoxic/HIF-1-active tumor cells during tumor growth and after radiation therapy, then exploit the information to develop innovative therapeutic strategies, and finally damage radioresistant cells. In this review, we overview problems caused by hypoxia/HIF-1-active cells in radiation therapy for cancer and introduce strategies to assess intratumoral hypoxia/HIF-1 activity. Full article
(This article belongs to the Special Issue Radiation and Cancers)

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